Influence of local anesthetics on molecular organization in phosphatidylethanolamine membranes
The influence of the local anesthetics tetracaine (TTC) and procaine (PRC) on bilayers of specifically deuterated phosphatidylethanolamines (PE) has been studied by /sup 2/H and /sup 31/P NMR. Dimyristoylphosphatidylethanolamines (DMPE), deuterated at positions 2, 4, and 14 of the sn-2 chain, position 2 of the sn-1 chain, and in the ethanolamine headgroup, were mixed 1:1 with a semisynthetic egg PE and the effect of measured quantities of TTC and PRC on the /sup 2/H quadrupole splittings, spin-lattice relaxation times, and /sup 31/P chemical shift anisotropy were observed. Experiments were performed at pH 5.5, when the anesthetics are primarily charged, and at pH 9.5, when they are uncharged. Tetracaine was observed to disorder the hydrocarbon region of the bilayer and to induce a conformational change in the PE headgroup. Conversely, procaine had little or no effect on the hydrocarbon region and induced only a small change in the headgroup. These conformational changes and disordering effects, when adjusted for anesthetic partitioning, are essentially independent of the charge on the anesthetic. However, at pH 5.5 and low TTC/PE molar ratios (less than 0.1), the /sup 2/H NMR spectra showed two lipid environments--one corresponding to free PE and the other to PE in contact with TTC. Continued addition of TTC resulted in the eventual disappearance of the free PE signal and the corresponding growth of the signal from PE in contact with TTC. At pH 9.5, when TTC is uncharged, only one signal is observed. In mixtures of PE and phosphatidylserine, a conformational change in the headgroup was noted which was similar to that seen in the pure PE; however, there was no evidence for slow lateral diffusion of the anesthetics.
- Research Organization:
- National Research Council of Canada, Ottawa
- OSTI ID:
- 5971614
- Journal Information:
- Mol. Pharmacol.; (United States), Vol. 26:2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANESTHETICS
BIOLOGICAL EFFECTS
CELL MEMBRANES
CONFORMATIONAL CHANGES
AMINES
COMPARATIVE EVALUATIONS
DEUTERIUM COMPOUNDS
NUCLEAR MAGNETIC RESONANCE
PHOSPHORUS 31
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAGNETIC RESONANCE
MEMBRANES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
RESONANCE
STABLE ISOTOPES
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550201 - Biochemistry- Tracer Techniques